Myocardial Infarction With Non-Obstructive Coronary Arteries Clinical Trial
— PROMISEOfficial title:
PROgnostic Value of Precision Medicine in Patients With Myocardial Infarction and Non-obStructive Coronary artEries: the PROMISE Trial.
The aim of our study is to evaluate if the use of a precision-medicine approach with a specific therapy tailored on the underlying pathogenic mechanism will improve the quality-of-life in MINOCA patients. The investigators further aim at investigating wherever a precision-medicine approach will improve the prognosis, healthcare related costs, and if that a different profile of plasma biomarkers and microRNAs may serve as diagnostic tools for detecting specific causes of MINOCA and to assess response to therapy. Finally, beyond its pivotal role in differential diagnosis, the investigators hypothesize that cardiac magnetic resonance (CMR) may provide a morphological and functional cardiac characterization as well as help in the prognostic stratification.
| Status | Recruiting |
| Enrollment | 180 |
| Est. completion date | July 2025 |
| Est. primary completion date | July 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Ability to give informed consent to the study - Age > 18y - MINOCA diagnosis, defined as: - Acute myocardial infarction (based on Fourth Universal Definition of Myocardial Infarction Criteria): - Evidence of non-obstructive coronary artery disease on angiography (i.e., no coronary artery stenosis >50%) in any major epicardial vessel. - No specific alternate diagnosis for the clinical presentation (i.e. non-ischemic causes of myocardial injury such as sepsis, pulmonary embolism, and myocarditis). Exclusion Criteria: - Inability or limited capacity to give informed consent to the study - Age < 18 y - Pregnant and breast-feeding women or patients considering becoming pregnant during the study period will be excluded. For women of childbearing potential, the use of a highly effective contraceptive measure is required in order to be included in the study. "Highly effective contraceptive" is defined in accordance with the recommendations of the Clinical Trial Facilitation Group as a contraceptive measure with a failure rate of less than 1% per year (https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG /2020_09_HMA_CTFG_Contraception_guidance_Version_1.1_updated.pdf). - Alternate diagnosis for the clinical presentation (i.e. non-ischemic causes of myocardial injury such as sepsis, pulmonary embolism, valve disease, hypertrophic cardiomyopathy and myocarditis). Also patients presenting with Takotsubo syndrome will be excluded. - Contraindication to contrast-enhanced CMR, eg, severe renal dysfunction (glomerular filtration rate <30 mL/min), non-CMR-compatible pacemaker or defibrillator. - Contraindication to drugs administrated: e.g a history of hypersensitivity to drugs administrated or its excipients, significant renal and/or hepatic disease. - Patients with comorbidities having an expected survival <1-year will be excluded. |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Centro Cardiologico Monzino | Milan | |
| Italy | Fondazione Policlinico Universitario A. Gemelli IRCCS | Rome | |
| Italy | IRCCS Policlinico San Donato | San Donato Milanese |
| Lead Sponsor | Collaborator |
|---|---|
| Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Centro Cardiologico Monzino, IRCCS Policlinico S. Donato |
Italy,
Crea F, Niccoli G. Myocardial Infarction With Nonobstructive Coronary Atherosclerosis: The Need for Precision Medicine. JACC Cardiovasc Imaging. 2019 Nov;12(11 Pt 1):2222-2224. doi: 10.1016/j.jcmg.2018.09.003. Epub 2018 Oct 17. No abstract available. — View Citation
Dastidar AG, Baritussio A, De Garate E, Drobni Z, Biglino G, Singhal P, Milano EG, Angelini GD, Dorman S, Strange J, Johnson T, Bucciarelli-Ducci C. Prognostic Role of CMR and Conventional Risk Factors in Myocardial Infarction With Nonobstructed Coronary Arteries. JACC Cardiovasc Imaging. 2019 Oct;12(10):1973-1982. doi: 10.1016/j.jcmg.2018.12.023. Epub 2019 Feb 13. — View Citation
Del Buono MG, Montone RA, Iannaccone G, Meucci MC, Rinaldi R, D'Amario D, Niccoli G. Diagnostic work-up and therapeutic implications in MINOCA: need for a personalized approach. Future Cardiol. 2021 Jan;17(1):149-154. doi: 10.2217/fca-2020-0052. Epub 2020 Jul 6. — View Citation
Fong SW, Few LL, See Too WC, Khoo BY, Nik Ibrahim NN, Yahaya SA, Yusof Z, Mohd Ali R, Abdul Rahman AR, Yvonne-Tee GB. Systemic and coronary levels of CRP, MPO, sCD40L and PlGF in patients with coronary artery disease. BMC Res Notes. 2015 Nov 14;8:679. doi: 10.1186/s13104-015-1677-8. — View Citation
Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25. — View Citation
Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11. — View Citation
Grodzinsky A, Arnold SV, Gosch K, Spertus JA, Foody JM, Beltrame J, Maddox TM, Parashar S, Kosiborod M. Angina Frequency After Acute Myocardial Infarction In Patients Without Obstructive Coronary Artery Disease. Eur Heart J Qual Care Clin Outcomes. 2015;1(2):92-99. doi: 10.1093/ehjqcco/qcv014. Epub 2015 Jul 23. — View Citation
Jaguszewski M, Osipova J, Ghadri JR, Napp LC, Widera C, Franke J, Fijalkowski M, Nowak R, Fijalkowska M, Volkmann I, Katus HA, Wollert KC, Bauersachs J, Erne P, Luscher TF, Thum T, Templin C. A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction. Eur Heart J. 2014 Apr;35(15):999-1006. doi: 10.1093/eurheartj/eht392. Epub 2013 Sep 17. — View Citation
Jespersen L, Abildstrom SZ, Hvelplund A, Galatius S, Madsen JK, Pedersen F, Hojberg S, Prescott E. Symptoms of angina pectoris increase the probability of disability pension and premature exit from the workforce even in the absence of obstructive coronary artery disease. Eur Heart J. 2013 Nov;34(42):3294-303. doi: 10.1093/eurheartj/eht395. Epub 2013 Sep 26. — View Citation
Li S, Lee C, Song J, Lu C, Liu J, Cui Y, Liang H, Cao C, Zhang F, Chen H. Circulating microRNAs as potential biomarkers for coronary plaque rupture. Oncotarget. 2017 Jul 18;8(29):48145-48156. doi: 10.18632/oncotarget.18308. — View Citation
Lindahl B, Baron T, Erlinge D, Hadziosmanovic N, Nordenskjold A, Gard A, Jernberg T. Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease. Circulation. 2017 Apr 18;135(16):1481-1489. doi: 10.1161/CIRCULATIONAHA.116.026336. Epub 2017 Feb 8. — View Citation
Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Camma G, Lanza GA, Crea F. Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J. 2018 Jan 7;39(2):91-98. doi: 10.1093/eurheartj/ehx667. — View Citation
Montone RA, Niccoli G, Russo M, Giaccari M, Del Buono MG, Meucci MC, Gurgoglione F, Vergallo R, D'Amario D, Buffon A, Leone AM, Burzotta F, Aurigemma C, Trani C, Liuzzo G, Lanza GA, Crea F. Clinical, angiographic and echocardiographic correlates of epicardial and microvascular spasm in patients with myocardial ischaemia and non-obstructive coronary arteries. Clin Res Cardiol. 2020 Apr;109(4):435-443. doi: 10.1007/s00392-019-01523-w. Epub 2019 Jul 3. Erratum In: Clin Res Cardiol. 2023 Apr;112(4):570. — View Citation
Niccoli G, Scalone G, Crea F. Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management. Eur Heart J. 2015 Feb 21;36(8):475-81. doi: 10.1093/eurheartj/ehu469. Epub 2014 Dec 18. — View Citation
Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation. 2015 Mar 10;131(10):861-70. doi: 10.1161/CIRCULATIONAHA.114.011201. Epub 2015 Jan 13. Erratum In: Circulation. 2015 May 12;131(19):e475. — View Citation
Planer D, Mehran R, Ohman EM, White HD, Newman JD, Xu K, Stone GW. Prognosis of patients with non-ST-segment-elevation myocardial infarction and nonobstructive coronary artery disease: propensity-matched analysis from the Acute Catheterization and Urgent Intervention Triage Strategy trial. Circ Cardiovasc Interv. 2014 Jun;7(3):285-93. doi: 10.1161/CIRCINTERVENTIONS.113.000606. Epub 2014 May 20. — View Citation
Rosano GMC, Tousoulis D, McFadden E, Clarke J, Davies GJ, Kaski JC. Effects of neuropeptide Y on coronary artery vasomotion in patients with microvascular angina. Int J Cardiol. 2017 Jul 1;238:123-127. doi: 10.1016/j.ijcard.2017.03.024. Epub 2017 Mar 16. — View Citation
Safdar B, Spatz ES, Dreyer RP, Beltrame JF, Lichtman JH, Spertus JA, Reynolds HR, Geda M, Bueno H, Dziura JD, Krumholz HM, D'Onofrio G. Presentation, Clinical Profile, and Prognosis of Young Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): Results From the VIRGO Study. J Am Heart Assoc. 2018 Jun 28;7(13):e009174. doi: 10.1161/JAHA.118.009174. — View Citation
Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, Lerman A, Cushman M, Kumbhani DJ, Arslanian-Engoren C, Bolger AF, Beltrame JF; American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Quality of Care and Outcomes Research. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019 Apr 30;139(18):e891-e908. doi: 10.1161/CIR.0000000000000670. — View Citation
Toyo-oka T, Aizawa T, Suzuki N, Hirata Y, Miyauchi T, Shin WS, Yanagisawa M, Masaki T, Sugimoto T. Increased plasma level of endothelin-1 and coronary spasm induction in patients with vasospastic angina pectoris. Circulation. 1991 Feb;83(2):476-83. doi: 10.1161/01.cir.83.2.476. — View Citation
* Note: There are 20 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Angina status | Angina status will be evaluated using the single-item "angina stability scale" and the two-item "angina frequence scale" of the Seattle Angina Questionnaire (SAQ). Scores are calculated by summing items within a dimension and transforming it to a 0-100 scale, where 0 is the worst and 100 the best possible level of health. * To reduce the risk of detection and performance bias, a team of 2 cardiologists blinded to group allocation and belonging to an external cardiology unit will submit and collate the questionnaires from study participants. |
1-year follow-up | |
| Primary | eattle Angina Questionnaire (SAQ) | Quality of life will be evaluated using the nine-item scale of "physical limitations scale", the three-item "treatment satisfaction scale" and two-item "disease perception scale" of the Seattle Angina Questionnaire (SAQ). Scores are calculated by summing items within a dimension and transforming it to a 0-100 scale, where 0 is the worst and 100 the best possible level of health. * To reduce the risk of detection and performance bias, a team of 2 cardiologists blinded to group allocation and belonging to an external cardiology unit will submit and collate the questionnaires from study participants. |
1-year follow-up | |
| Secondary | Rates of major adverse cardiovascular events | Rates of major adverse cardiovascular events (MACE; composite of all-cause mortality; re-hospitalization for myocardial infarction, stroke or heart failure; repeated coronary angiography) will be evaluated at 1-year follow-up in MINOCA patients. | 1-year follow-up | |
| Secondary | Healthcare primary related-costs | Healthcare primary related costs will be evaluated as mean costs (including procedures, tests, medicines). | 1-year follow-up | |
| Secondary | Healthcare secondary related-costs | Healthcare secondary related-costs will be evaluated as mean quality adjusted life year (QALY) gained. | 1-year follow-up | |
| Secondary | Healthcare secondary related-costs | Healthcare secondary related-costs will be evaluated as the incremental cost-effectiveness ratio (ICER) expressed as the cost per QALY. | 1-year follow-up | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers: -miRNAs (miR-16, miR-26a, miR-145, miR-222, miR-155-5p, miR-483-5p, miR-45): to measure miRNA reverse transcriptase polymerase chain reaction (RT-PCR) will be employed and results will be expressed in relative expression (2-??CT Method). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers: -Endothelin 1: It will be assessed through ELISA immunoassay and results will be expressed in Picograms per millilitre (pg/mL). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers: -Neuropeptide Y: It will be assessed through ELISA immunoassay and results will be expressed in Picograms per millilitre (pg/mL). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers: -soluble CD40 ligand: It will be assessed through ELISA immunoassay and results will be expressed in Picograms per millilitre (pg/mL). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of left and right ventricle volumes (in ml or ml/m2). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of myocardial edema using T2-weighted sequences and a 17 segments assessment model of cardiac segmentation. | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of defect of perfusion using first pass perfusion sequences and a 17 segments assessment model of cardiac segmentation. | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of fibrosis using late gadolinium enhancement sequences and a 17 segments assessment model of cardiac segmentation (estimated as LGE % of the cardiac segment involved). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of myocardial infarct size (estimated as grams or % of left ventricular myocardial mass). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Functional cardiac characterization will be assessed by measurement of right and left ventricles eject fraction (estimated as %). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Functional cardiac characterization will be assesaed by measurement of regional kinetic abnormalities using a 17 segments assessment model of cardiac segmentation. | from day 3 to day 7 from the acute coronary event |
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